ID   IRT1_ARATH              Reviewed;         347 AA.
AC   Q38856; Q8LBP0;
DT   26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT   31-MAY-2011, sequence version 2.
DT   27-MAR-2024, entry version 168.
DE   RecName: Full=Fe(2+) transport protein 1;
DE   AltName: Full=Fe(II) transport protein 1;
DE   AltName: Full=Iron-regulated transporter 1;
DE   Flags: Precursor;
GN   Name=IRT1; OrderedLocusNames=At4g19690; ORFNames=T16H5.50;
OS   Arabidopsis thaliana (Mouse-ear cress).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis.
OX   NCBI_TaxID=3702;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=cv. Columbia;
RX   PubMed=10617198; DOI=10.1038/47134;
RA   Mayer K.F.X., Schueller C., Wambutt R., Murphy G., Volckaert G., Pohl T.,
RA   Duesterhoeft A., Stiekema W., Entian K.-D., Terryn N., Harris B.,
RA   Ansorge W., Brandt P., Grivell L.A., Rieger M., Weichselgartner M.,
RA   de Simone V., Obermaier B., Mache R., Mueller M., Kreis M., Delseny M.,
RA   Puigdomenech P., Watson M., Schmidtheini T., Reichert B., Portetelle D.,
RA   Perez-Alonso M., Boutry M., Bancroft I., Vos P., Hoheisel J.,
RA   Zimmermann W., Wedler H., Ridley P., Langham S.-A., McCullagh B.,
RA   Bilham L., Robben J., van der Schueren J., Grymonprez B., Chuang Y.-J.,
RA   Vandenbussche F., Braeken M., Weltjens I., Voet M., Bastiaens I., Aert R.,
RA   Defoor E., Weitzenegger T., Bothe G., Ramsperger U., Hilbert H., Braun M.,
RA   Holzer E., Brandt A., Peters S., van Staveren M., Dirkse W., Mooijman P.,
RA   Klein Lankhorst R., Rose M., Hauf J., Koetter P., Berneiser S., Hempel S.,
RA   Feldpausch M., Lamberth S., Van den Daele H., De Keyser A., Buysshaert C.,
RA   Gielen J., Villarroel R., De Clercq R., van Montagu M., Rogers J.,
RA   Cronin A., Quail M.A., Bray-Allen S., Clark L., Doggett J., Hall S.,
RA   Kay M., Lennard N., McLay K., Mayes R., Pettett A., Rajandream M.A.,
RA   Lyne M., Benes V., Rechmann S., Borkova D., Bloecker H., Scharfe M.,
RA   Grimm M., Loehnert T.-H., Dose S., de Haan M., Maarse A.C., Schaefer M.,
RA   Mueller-Auer S., Gabel C., Fuchs M., Fartmann B., Granderath K., Dauner D.,
RA   Herzl A., Neumann S., Argiriou A., Vitale D., Liguori R., Piravandi E.,
RA   Massenet O., Quigley F., Clabauld G., Muendlein A., Felber R., Schnabl S.,
RA   Hiller R., Schmidt W., Lecharny A., Aubourg S., Chefdor F., Cooke R.,
RA   Berger C., Monfort A., Casacuberta E., Gibbons T., Weber N., Vandenbol M.,
RA   Bargues M., Terol J., Torres A., Perez-Perez A., Purnelle B., Bent E.,
RA   Johnson S., Tacon D., Jesse T., Heijnen L., Schwarz S., Scholler P.,
RA   Heber S., Francs P., Bielke C., Frishman D., Haase D., Lemcke K.,
RA   Mewes H.-W., Stocker S., Zaccaria P., Bevan M., Wilson R.K.,
RA   de la Bastide M., Habermann K., Parnell L., Dedhia N., Gnoj L., Schutz K.,
RA   Huang E., Spiegel L., Sekhon M., Murray J., Sheet P., Cordes M.,
RA   Abu-Threideh J., Stoneking T., Kalicki J., Graves T., Harmon G.,
RA   Edwards J., Latreille P., Courtney L., Cloud J., Abbott A., Scott K.,
RA   Johnson D., Minx P., Bentley D., Fulton B., Miller N., Greco T., Kemp K.,
RA   Kramer J., Fulton L., Mardis E., Dante M., Pepin K., Hillier L.W.,
RA   Nelson J., Spieth J., Ryan E., Andrews S., Geisel C., Layman D., Du H.,
RA   Ali J., Berghoff A., Jones K., Drone K., Cotton M., Joshu C., Antonoiu B.,
RA   Zidanic M., Strong C., Sun H., Lamar B., Yordan C., Ma P., Zhong J.,
RA   Preston R., Vil D., Shekher M., Matero A., Shah R., Swaby I.K.,
RA   O'Shaughnessy A., Rodriguez M., Hoffman J., Till S., Granat S., Shohdy N.,
RA   Hasegawa A., Hameed A., Lodhi M., Johnson A., Chen E., Marra M.A.,
RA   Martienssen R., McCombie W.R.;
RT   "Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana.";
RL   Nature 402:769-777(1999).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=cv. Columbia;
RX   PubMed=27862469; DOI=10.1111/tpj.13415;
RA   Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
RA   Town C.D.;
RT   "Araport11: a complete reannotation of the Arabidopsis thaliana reference
RT   genome.";
RL   Plant J. 89:789-804(2017).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA   Brover V.V., Troukhan M.E., Alexandrov N.A., Lu Y.-P., Flavell R.B.,
RA   Feldmann K.A.;
RT   "Full-length cDNA from Arabidopsis thaliana.";
RL   Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 4-347 (ISOFORM 1), AND CHARACTERIZATION.
RC   STRAIN=cv. Landsberg erecta;
RX   PubMed=8643627; DOI=10.1073/pnas.93.11.5624;
RA   Eide D., Broderius M., Fett J., Guerinot M.L.;
RT   "A novel iron-regulated metal transporter from plants identified by
RT   functional expression in yeast.";
RL   Proc. Natl. Acad. Sci. U.S.A. 93:5624-5628(1996).
RN   [5]
RP   CHARACTERIZATION, AND METAL-BINDING.
RX   PubMed=9784581; DOI=10.1007/s002329900442;
RA   Eng B.H., Guerinot M.L., Eide D., Saier M.H. Jr.;
RT   "Sequence analyses and phylogenetic characterization of the ZIP family of
RT   metal ion transport proteins.";
RL   J. Membr. Biol. 166:1-7(1998).
RN   [6]
RP   BROAD CATION RANGE.
RX   PubMed=10394943; DOI=10.1023/a:1026438615520;
RA   Korshunova Y.O., Eide D., Clark W.G., Guerinot M.L., Pakrasi H.B.;
RT   "The IRT1 protein from Arabidopsis thaliana is a metal transporter with a
RT   broad substrate range.";
RL   Plant Mol. Biol. 40:37-44(1999).
RN   [7]
RP   MUTAGENESIS OF HIS-104; ASP-108; GLU-111; ASP-144; HIS-205; SER-206;
RP   HIS-232 AND GLU-236.
RX   PubMed=11035780; DOI=10.1073/pnas.210214197;
RA   Rogers E.E., Eide D.J., Guerinot M.L.;
RT   "Altered selectivity in an Arabidopsis metal transporter.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:12356-12360(2000).
RN   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=12084823; DOI=10.1105/tpc.001388;
RA   Vert G., Grotz N., Dedaldechamp F., Gaymard F., Guerinot M.L., Briat J.-F.,
RA   Curie C.;
RT   "IRT1, an Arabidopsis transporter essential for iron uptake from the soil
RT   and for plant growth.";
RL   Plant Cell 14:1223-1233(2002).
RN   [9]
RP   SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-154 AND LYS-179, UBIQUITINATION AT
RP   LYS-154 AND LYS-179, AND INDUCTION BY IRON STARVATION.
RX   PubMed=21628566; DOI=10.1073/pnas.1100659108;
RA   Barberon M., Zelazny E., Robert S., Conejero G., Curie C., Friml J.,
RA   Vert G.;
RT   "Monoubiquitin-dependent endocytosis of the iron-regulated transporter 1
RT   (IRT1) transporter controls iron uptake in plants.";
RL   Proc. Natl. Acad. Sci. U.S.A. 108:E450-458(2011).
RN   [10]
RP   INTERACTION WITH FREE1, AND SUBCELLULAR LOCATION.
RX   PubMed=24843126; DOI=10.1073/pnas.1402262111;
RA   Barberon M., Dubeaux G., Kolb C., Isono E., Zelazny E., Vert G.;
RT   "Polarization of IRON-REGULATED TRANSPORTER 1 (IRT1) to the plant-soil
RT   interface plays crucial role in metal homeostasis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 111:8293-8298(2014).
CC   -!- FUNCTION: High-affinity iron transporter that plays a key role in the
CC       uptake of iron from the rhizosphere across the plasma membrane in the
CC       root epidermal layer. Acts as the principal regulator of iron
CC       homeostasis in planta. Also mediates the heavy metals uptake under
CC       iron-deficiency by its ability to transport cobalt, cadmium, manganese
CC       and/or zinc ions. {ECO:0000269|PubMed:12084823}.
CC   -!- SUBUNIT: Interacts with FREE1. {ECO:0000269|PubMed:24843126}.
CC   -!- INTERACTION:
CC       Q38856; P59263: UBQ16; NbExp=3; IntAct=EBI-15928951, EBI-1541543;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12084823,
CC       ECO:0000269|PubMed:21628566, ECO:0000269|PubMed:24843126}; Multi-pass
CC       membrane protein {ECO:0000269|PubMed:12084823}. Early endosome
CC       {ECO:0000269|PubMed:21628566, ECO:0000269|PubMed:24843126}. Golgi
CC       apparatus, trans-Golgi network {ECO:0000269|PubMed:21628566,
CC       ECO:0000269|PubMed:24843126}. Vacuole {ECO:0000269|PubMed:21628566}.
CC       Note=Cycles constitutively between early endosomes and the plasma
CC       membrane and is targeted to the vacuole for degradation.
CC       {ECO:0000269|PubMed:21628566}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q38856-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q38856-2; Sequence=VSP_008361, VSP_008362;
CC   -!- TISSUE SPECIFICITY: Expressed in the external cell layers of the root
CC       including the lateral branching zone. Also detected in flowers before
CC       pollination. {ECO:0000269|PubMed:12084823}.
CC   -!- INDUCTION: In roots by iron starvation. {ECO:0000269|PubMed:21628566}.
CC   -!- PTM: Monoubiquitinated on several Lys residues. Monoubiquitination
CC       controls trafficking from the plasma membrane and targeting to the
CC       vacuole. {ECO:0000269|PubMed:21628566}.
CC   -!- DISRUPTION PHENOTYPE: Plants exhibit a lethal chlorotic phenotype.
CC       {ECO:0000269|PubMed:12084823}.
CC   -!- MISCELLANEOUS: Inhibited by cadmium and Fe(2+) ions and at 100-fold
CC       excess inhibited by cobalt, manganese and zinc ions.
CC   -!- MISCELLANEOUS: The availability of secondary non-iron metal substrates
CC       (Zn, Mn, and Co) controls the localization of IRT1 between the outer
CC       polar domain of the plasma membrane and early endosome/trans-Golgi
CC       network in root epidermal cells. {ECO:0000269|PubMed:24843126}.
CC   -!- MISCELLANEOUS: [Isoform 2]: May be due to an intron retention.
CC       {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the ZIP transporter (TC 2.A.5) family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB01678.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=CAA19686.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=CAB78971.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AL024486; CAA19686.1; ALT_INIT; Genomic_DNA.
DR   EMBL; AL161551; CAB78971.1; ALT_INIT; Genomic_DNA.
DR   EMBL; CP002687; AEE84216.1; -; Genomic_DNA.
DR   EMBL; CP002687; AEE84217.1; -; Genomic_DNA.
DR   EMBL; AY087095; AAM64655.1; -; mRNA.
DR   EMBL; U27590; AAB01678.1; ALT_INIT; mRNA.
DR   PIR; T04750; T04750.
DR   RefSeq; NP_567590.3; NM_118089.4. [Q38856-1]
DR   RefSeq; NP_849546.1; NM_179215.2. [Q38856-2]
DR   AlphaFoldDB; Q38856; -.
DR   BioGRID; 13006; 3.
DR   DIP; DIP-60391N; -.
DR   IntAct; Q38856; 1.
DR   STRING; 3702.Q38856; -.
DR   TCDB; 2.A.5.1.2; the zinc (zn(2+))-iron (fe(2+)) permease (zip) family.
DR   iPTMnet; Q38856; -.
DR   PaxDb; 3702-AT4G19690-2; -.
DR   ProteomicsDB; 247047; -. [Q38856-1]
DR   EnsemblPlants; AT4G19690.1; AT4G19690.1; AT4G19690. [Q38856-2]
DR   EnsemblPlants; AT4G19690.2; AT4G19690.2; AT4G19690. [Q38856-1]
DR   GeneID; 827713; -.
DR   Gramene; AT4G19690.1; AT4G19690.1; AT4G19690. [Q38856-2]
DR   Gramene; AT4G19690.2; AT4G19690.2; AT4G19690. [Q38856-1]
DR   KEGG; ath:AT4G19690; -.
DR   Araport; AT4G19690; -.
DR   TAIR; AT4G19690; IRT1.
DR   eggNOG; KOG1558; Eukaryota.
DR   HOGENOM; CLU_027089_3_0_1; -.
DR   InParanoid; Q38856; -.
DR   OMA; FHWTKAS; -.
DR   OrthoDB; 1112460at2759; -.
DR   BioCyc; ARA:AT4G19690-MONOMER; -.
DR   BioCyc; MetaCyc:AT4G19690-MONOMER; -.
DR   PRO; PR:Q38856; -.
DR   Proteomes; UP000006548; Chromosome 4.
DR   ExpressionAtlas; Q38856; baseline and differential.
DR   GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005768; C:endosome; IDA:TAIR.
DR   GO; GO:0005886; C:plasma membrane; IDA:TAIR.
DR   GO; GO:0005802; C:trans-Golgi network; IDA:TAIR.
DR   GO; GO:0005773; C:vacuole; IEA:UniProtKB-SubCell.
DR   GO; GO:0005375; F:copper ion transmembrane transporter activity; IGI:TAIR.
DR   GO; GO:0005381; F:iron ion transmembrane transporter activity; IGI:TAIR.
DR   GO; GO:0005385; F:zinc ion transmembrane transporter activity; IEA:InterPro.
DR   GO; GO:0030001; P:metal ion transport; IMP:TAIR.
DR   GO; GO:0015675; P:nickel cation transport; IMP:TAIR.
DR   GO; GO:0009617; P:response to bacterium; IEP:TAIR.
DR   InterPro; IPR003689; ZIP.
DR   InterPro; IPR004698; Zn/Fe_permease_fun/pln.
DR   NCBIfam; TIGR00820; zip; 1.
DR   PANTHER; PTHR11040:SF159; FE(2+) TRANSPORT PROTEIN 1; 1.
DR   PANTHER; PTHR11040; ZINC/IRON TRANSPORTER; 1.
DR   Pfam; PF02535; Zip; 1.
DR   Genevisible; Q38856; AT.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Endosome; Golgi apparatus;
KW   Ion transport; Iron; Iron transport; Isopeptide bond; Membrane;
KW   Reference proteome; Signal; Transmembrane; Transmembrane helix; Transport;
KW   Ubl conjugation; Vacuole.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   CHAIN           23..347
FT                   /note="Fe(2+) transport protein 1"
FT                   /id="PRO_0000041636"
FT   TOPO_DOM        23..52
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        53..73
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        74..84
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        85..105
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        106..125
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        126..146
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        147..192
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        193..213
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        214..224
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        225..245
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        246..254
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        255..275
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        276..286
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        287..307
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        308..326
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        327..347
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   CROSSLNK        154
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000305|PubMed:21628566"
FT   CROSSLNK        179
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000305|PubMed:21628566"
FT   VAR_SEQ         198..211
FT                   /note="LELGIIVHSVVIGL -> RTHIYTYRISLYFK (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.3"
FT                   /id="VSP_008361"
FT   VAR_SEQ         212..347
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.3"
FT                   /id="VSP_008362"
FT   MUTAGEN         104
FT                   /note="H->A: Suppresses transport."
FT                   /evidence="ECO:0000269|PubMed:11035780"
FT   MUTAGEN         108
FT                   /note="D->A: Abolishes iron and manganese transport."
FT                   /evidence="ECO:0000269|PubMed:11035780"
FT   MUTAGEN         111
FT                   /note="E->A: Abolishes zinc transport. Abolishes iron and
FT                   manganese transport; when associated with A-108."
FT                   /evidence="ECO:0000269|PubMed:11035780"
FT   MUTAGEN         144
FT                   /note="D->A: Abolishes iron and manganese transport.
FT                   Reduces cadmium transport."
FT                   /evidence="ECO:0000269|PubMed:11035780"
FT   MUTAGEN         154
FT                   /note="K->R: Suppresses ubiquitination and loss of
FT                   activity; when associated with R-179."
FT                   /evidence="ECO:0000269|PubMed:21628566"
FT   MUTAGEN         179
FT                   /note="K->R: Suppresses ubiquitination and loss of
FT                   activity; when associated with R-154."
FT                   /evidence="ECO:0000269|PubMed:21628566"
FT   MUTAGEN         205
FT                   /note="H->A,E: Suppresses transport."
FT                   /evidence="ECO:0000269|PubMed:11035780"
FT   MUTAGEN         206
FT                   /note="S->A: Suppresses transport."
FT                   /evidence="ECO:0000269|PubMed:11035780"
FT   MUTAGEN         232
FT                   /note="H->A: Suppresses transport."
FT                   /evidence="ECO:0000269|PubMed:11035780"
FT   MUTAGEN         236
FT                   /note="E->A: Suppresses transport."
FT                   /evidence="ECO:0000269|PubMed:11035780"
SQ   SEQUENCE   347 AA;  36727 MW;  1F94091668994EA4 CRC64;
     MASNSALLMK TIFLVLIFVS FAISPATSTA PEECGSESAN PCVNKAKALP LKVIAIFVIL
     IASMIGVGAP LFSRNVSFLQ PDGNIFTIIK CFASGIILGT GFMHVLPDSF EMLSSICLEE
     NPWHKFPFSG FLAMLSGLIT LAIDSMATSL YTSKNAVGIM PHGHGHGHGP ANDVTLPIKE
     DDSSNAQLLR YRVIAMVLEL GIIVHSVVIG LSLGATSDTC TIKGLIAALC FHQMFEGMGL
     GGCILQAEYT NMKKFVMAFF FAVTTPFGIA LGIALSTVYQ DNSPKALITV GLLNACSAGL
     LIYMALVDLL AAEFMGPKLQ GSIKMQFKCL IAALLGCGGM SIIAKWA
//